S1618 TISAGENLECLEUCEL APPEARS EFFECTIVE AND SAFE IN PEDIATRIC AND YOUNG ADULT PATIENTS WITH RELAPSED/REFRACTORY ACUTE LYMPHOBLASTIC LEUKEMIA WITH HIGH‐RISK CYTOGENETIC ABNORMALITIES
Notice bibliographique
Résumé
Background: Cytogenetic and molecular genetic findings at diagnosis constitute important independent prognostic and risk stratification factors in B‐cell acute lymphoblastic leukemia (ALL). Certain alterations signify high‐risk (HR) cytogenetic abnormalities and are associated with poorer prognosis and inferior outcomes, particularly in patients (pts) with relapsed/refractory (r/r) disease. Tisagenlecleucel is an anti‐CD19 chimeric antigen receptor (CAR)‐T cell therapy approved in multiple countries/regions for the treatment of pediatric and young adult pts with r/r ALL (r/r pALL). Tisagenlecleucel has demonstrated high rates of durable responses and a manageable safety profile in the ELIANA and ENSIGN trials. Aims: We analyzed outcomes in a subgroup of pts from the ELIANA and ENSIGN studies with reported HR cytogenetic abnormalities at enrollment, namely: hypodiploidy; t(9;22)(q34;q11.2)/ BCR‐ABL1 ; KMT2A (MLL) rearrangement; intrachromosomal amplification of chromosome 21 (iAMP21); t(17;19)(q23;p13), encoding TCF3‐HLF fusion; BCR‐ABL1‐like; CRLF2 rearrangement; and/or TP53 mutation/deletion. Methods: ELIANA and ENSIGN are single‐arm, multicenter, phase 2 trials of tisagenlecleucel in pts with r/r pALL. The primary endpoint is overall remission rate (ORR: complete remission [CR] + CR with incomplete blood count recovery [CRi]) within 3 months per independent review committee (IRC) assessment. In this subgroup analysis, pooled efficacy and safety data from ELIANA and ENSIGN are presented for pts with HR cytogenetic abnormalities. Results: A total of 29/137 infused pts (ELIANA 13/79, ENSIGN 16/58) were identified with HR cytogenetic abnormalities (Table). Median age was 12 years (range, 3–21 years); median previous lines of therapy was 3 (range, 1–8); and 15/29 pts received at least 1 prior hematopoietic stem cell transplant. Among all infused pts (full analysis set), 19/29 (65.5%) pts with HR cytogenetic abnormalities (vs 81/108 [75.0%] pts without the aforementioned HR cytogenetic abnormalities) from this pooled data set achieved confirmed remission per IRC assessment, and 18/19 of these responding pts were negative for minimal residual disease by flow cytometry. Of the remaining 10 pts, 4 did not reach Day 28 assessment at data cutoff, 3 died before Day 28 assessment (1 each from progressive leukemia, cerebral hemorrhage, and embolic stroke), 2 had missing assessments, and 1 did not respond to therapy. Among the 19 responding pts, 4 relapsed; the median duration of response was not reached, with estimated relapse‐free probability at 12 and 24 months after remission onset of 74.6% (vs 61.7% and 58.5%, respectively, in pts without HR cytogenetic abnormalities). Median overall survival in pts with HR cytogenetic abnormalities was not reached, with estimated 12‐ and 24‐month survival probability of 74.9% and 66.6%, respectively (vs 70.7% and 58.8%, respectively, in pts without HR cytogenetic abnormalities). Rates of select adverse events that occurred within 8 weeks after infusion in pts with HR cytogenetic abnormalities were: cytokine release syndrome (grade 3, 17.2%; grade 4, 27.6%), infections (grade 3, 13.8%; grade 4, 3.4%), cytopenias not resolved by Day 28 (grade 3, 17.2%; grade 4; 13.8%), and neurological events (grade 3, 3.4%; no grade 4 events). Summary/Conclusion: In pts with HR cytogenetic abnormalities with historically poor prognosis, tisagenlecleucel appears effective, with high rates of durable responses, prolonged survival, and a manageable safety profile. image Clinical trial information: NCT02435849; NCT02228096.
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».